Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis in cultured lung cancer cells. However, there is little information on the involvement of microRNAs (miRNAs) in its effects. miRNA microarray analysis and polymerase-chain-reaction analysis of miRNAs revealed that treatment of human lung cancer A549 cells with apigenin up-regulated the level of miR-34a-5p. Furthermore, mRNA microarray analysis and the results of three microRNA target prediction tools showed that Snail Family Transcriptional Repressor 1 (SNAI1), which inhibits the induction of apoptosis, had its mRNA expression down-regulated in A549 cells treated with apigenin. Our findings suggest that apigenin might induce apoptosis by down-regulation of SNAI1 through up-regulation of miR-34a-5p in A549 cells.
7 July 2016 in Development, Growth & Differentiation
Zfp318, a mouse gene with a Cys2/His2 zinc finger motif, is mainly expressed in germ cells in the testis. It encodes two alternative transcripts, which regulate androgen receptor‐mediated transcriptional activation or repression by overexpression of them. However, the role of Zfp318 is still obscure in vivo, especially in spermatogenesis. To elucidate the role of Zfp318 during gamete production, we established a knockout mouse line. Zfp318‐null male mice exhibited infertility, whereas Zfp318‐null female mice displayed normal fertility. ZFP318 was expressed during multiple stages of spermatogenesis, from spermatocytes to round spermatids. The nuclei of secondary spermatocytes showed high levels of expression. Histological analysis and quantitative analysis of DNA content showed decreased numbers of both spermatids in the seminiferous tubules and mature spermatozoa in the epididymides of Zfp318‐null mice. These results suggest that Zfp318 is expressed as a functional protein in testicular germ cells and plays an important role in meiosis during spermatogenesis.
Background/Aim: Genistein (4′, 5, 7-trihydroxyisoflavone) and daidzein (4′, 7-dihydroxyisoflavone) are isoflavones derived from soybean and have anti-cancer effects in various cells. However, the effects of genistein and daidzein on the human osteosarcoma cell line Saos-2 has not been investigated before. Materials and Methods: Human osteosarcoma Saos-2 cells were treated with genistein for 24 and 48 hours. Cytotoxicity and apoptosis were measured. Results: Genistein significantly inhibited proliferation of Saos-2 cells stronger than daidzein in a dose-dependent manner (0 to 80 μM). Genistein also significantly suppressed Saos-2 cell viability in a dose-dependent manner (0 to 100 μM). In contrast, daidzein did not affect Saos-2 cell viability. Real-time PCR revealed that genistein caused G1-arrest by increasing the expression of p21 and p27 mRNAs in Saos-2 cells. In addition, genistein induced apoptosis through the up-regulation of effector caspase-3/7 activity in Saos-2 cells. Genistein also enhanced initiator caspase-9 and TNF-α mRNA expression in cells. Conclusion: Genistein may inhibit proliferation through the up-regulation of p21 and p27 and viability by inducing apoptosis in Saos-2 cells.
Carnosic acid is a major polyphenol of rosemary and possesses potent anti-oxidant effects. The present study was designed to evaluate in vitro and in vivo effects of carnosic acid on bone formation and maintenance. Carnosic acid attenuated H2O2 levels in osteoblastic MC3T3-E1 cells. This compound also inhibited the indices of osteoblast differentiation, such as alkaline phosphatase activity and calcium deposition in osteoblastic MC3T3-E1 cells at concentrations of 3–10μM. Furthermore, it decreased the formation of multinucleated osteoclasts in co-cultures of mouse spleen cells with ST2 cells. In addition, we identified a molecular pathway of osteoclast differentiation mediated by carnosic acid, which led to inhibition of the expression of receptor activator of nuclear factor-κB ligand in ST2 cells. Interestingly, intraperitoneal injection of carnosic acid at 10mg/kg body weight did not significantly affect trabecular bone loss in the femurs of ovariectomized mice. Our findings indicate that carnosic acid may be used as an effective remedy in the treatment of the symptoms of osteoporosis